5-132490150-T-G

Position:

• chr5-132490150-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002198.3(IRF1):​c.-6+395A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,194 control chromosomes in the GnomAD database, including 21,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (20996 hom., cov: 33)
  • Exomes 𝑓: 0.39 (8 hom.)
• Consequence: IRF1 NM_002198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

Genes affected

IRF1 (HGNC:6116): (interferon regulatory factor 1) The protein encoded by this gene is a transcriptional regulator and tumor suppressor, serving as an activator of genes involved in both innate and acquired immune responses. The encoded protein activates the transcription of genes involved in the body's response to viruses and bacteria, playing a role in cell proliferation, apoptosis, the immune response, and DNA damage response. This protein represses the transcription of several other genes. As a tumor suppressor, it both suppresses tumor cell growth and stimulates an immune response against tumor cells. Defects in this gene have been associated with gastric cancer, myelogenous leukemia, and lung cancer. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF1	NM_002198.3	c.-6+395A>C		intron_variant		ENST00000245414.9	NP_002189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF1	ENST00000245414.9	c.-6+395A>C		intron_variant		1	NM_002198.3	ENSP00000245414	P1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78611 AN: 151966 Hom.: 20958 Cov.: 33

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.391 AC: 43 AN: 110 Hom.: 8 Cov.: 0 AF XY: 0.395 AC XY: 30 AN XY: 76

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.518 AC: 78710 AN: 152084 Hom.: 20996 Cov.: 33 AF XY: 0.525 AC XY: 39032 AN XY: 74354

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.489

Alfa AF: 0.394 Hom.: 2000

Bravo AF: 0.522

Asia WGS AF: 0.618 AC: 2149 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.7
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070721; hg19: chr5-131825842;